The present invention relates to an ion source suited for ionizing a sample existing in a liquid to introduce the ionized sample into a mass spectrometer, and a mass spectrometer using the ion source.
Using capillary electrophoresis (CE) or the liquid chromatograph (LC) it is easy to separate a sample existing in a solution but difficult to identify the kinds of samples separated. On the other hand, a mass spectrometer (MS) can identify the separated sample with high accuracy. Thus, when it is intended to separate and analyze a plurality of biological substances dissolved in a solvent such as water, there is generally used capillary electrophoresis in combination with a mass spectrometer (CE/MS) or liquid chromatograph in combination with a mass spectrometer (LC/MS) which is constructed by combining the capillary electrophoresis or the liquid chromatograph with the mass spectrometer.
In order to analyze the sample, which is separated by the capillary electrophoresis or the liquid chromatograph, using the mass spectrometer, it is necessary to transform the sample molecules in the solution into gaseous ions, i.e. gaseous particles or gaseous materials. A conventional technique for producing such ions is known as the ion spray method (as disclosed in Analytical Chemistry, Vol. 59, No. 22, Nov. 15, 1987, pp. 2642-2646). In the ion spray method, the gas is introduced along the outer circumference of a capillary, and a high voltage (e.g. 3 to 6 kV) is applied between the capillary to be fed with the sample solution and an aperture (e.g. the sampling orifice) for introducing the ions into the mass spectrometer, so that an intense electric field is established at the capillary tip. By the electrospray phenomenon established by that construction, there are produced fine charged droplets, which are evaporated by the aforementioned gas to form gaseous ions, i.e. gaseous particles or gaseous materials. The ions thus formed are introduced via the sampling orifice into the mass spectrometer so that they are mass-analyzed. The aforementioned gas promotes the atomization of the charged droplets and suppresses the discharge at the tip of the capillary.
Another conventional technique is known as the electrospray method of ionizing a solution with no gas flow at a flow rate of 10 μL/min (microliters/minute) to the capillary (as disclosed in Journal of Physical Chemistry, Vol. 88, No. 20, 1984, pp. 4451-4459). The electrospray method is different from the ion spray method but has the same ionization principle as that of the ion spray method.
A further conventional technique is known as the atmospheric pressure chemical ionization method (as disclosed in Analytical Chemistry, Vol. 54, No. 1, January 1982, pp. 143-146). In the atmosphere pressure chemical ionization method there is disposed in the vicinity of the tip of the heated capillary an electrode for generating a corona discharge to ionize the volatile molecules sprayed under atmospheric pressure.
The various conventional spray ionization methods described above in order to achieve a high ionization efficiency, it is necessary to form fine charged droplets having a diameter no more than about 10 nm.
In the conventional techniques described above, a high voltage is applied around the sampling orifice. This application makes it necessary to avoid an electric shock, thus causing a problem that the instrument has a complicated structure. Since the high voltage is applied to the capillary tip in the CE/MS, a higher voltage has to be applied so that the electrophoresis of the sample may be effected in the capillary electrophoresis instrument.
Moreover, the electrospray phenomenon is so seriously influenced by contamination at the tip of the capillary and on the surface of the sampling orifice that once the spray of the sample solution is interrupted, the electrospray method or the ion spray method detects different ion intensities with a poor reproducibility even if the spray is reopened under the identical conditions. In order to maximize the ion intensity detected, therefore, the troublesome operations of finely adjusting the capillary position or cleaning the capillary tip and the sampling orifice surface are required each time the spraying operation is reopened. As a result, the structure of the instrument is so complicated for avoiding electric shock that the operations are obstructed.
In the conventional techniques described above, moreover, the sample solution has to be mixed with volatile molecules such as alcohol or ammonia as the solvent. It has been empirically known that no electrospray phenomenon occurs when the solvent used has a low electric conductivity, and that the electric conductivity of the sample solution has to be within 10−13 to 10−15 (Ω·cm)−1 so as to establish the electrospray phenomenon. Thus, there arises a problem that so long as those conditions are not satisfied, the electrospray phenomenon does not stably occur to limit the selection of the solvent.
Further, since a high voltage is applied between the capillary and the sampling orifice, a discharge may occur around the ion source to make it difficult to use an inflammable solvent. If the kind of solvent to be used is thus limited, the substance to be measured may be unable to be separated by the capillary electrophoresis or the liquid chromatograph.